Heme proteins are the basis of physiological electron transport(cytochromes), oxygen transport and storage (hemoglobin, myoglobin), oxygen reduction (cytochrome oxidase), oxidation of foreign substances (cycochrome P-450) and protection of the organism from the deleterious effects of peroxides (peroxidase). This proposal addresses the specific questions of structure and reactivity in monohistidine (e.g. hemoglobin, myoglobin, peroxidase) and bishistidine (e.g. cytochrome b) heme proteins. We propose that the axial histidine residues are not simply structural components of the heme proteins, but are actively involved in the biochemistry of these species. It is difficult to study the histidine-heme interaction in proteins themselves, because one has no control over either the histidine-heme interaction in the proteins themselves, because one has no control over either the orientation or the hydrogen bonding of the histidine in the protein. One solution to this problem is to use model heme complexes to mimic the behavior of the proteins. We will synthesize and study "chelated hemes". these compounds have the axial histidine (imidazole ring) covalently attached to the heme through a chelating arm, which forces a particular orientation. They can be synthesized by attaching the chelating arm to the C-5 position of the imidazole ring, thus allowing hydrogen bonding of the NH proton (insert). The chelating arm can also be attached to the N-1 nitrogen, thus eliminating the NH proton and precluding any hydrogen bonding. We will use these models to determine the effect of the imidazole-heme orientation and hydrogen bonding on the NMR and EPR spectra of the hemes. We will also study the effect of orientation and hydrogen bonding on the redox potential and rate of electron transfer. In particular, we will study the mechanism of hemeglobin autoxidation and the role of the axial histidine in intramolecular electron transfer. Our long-term goal is to understand the factors which control electron transfer in heme proteins.